Pharmacy and Pharmaceutical Sciences Commons^™

Characterization Of Drug-Loaded Milled Extrudate Particles Produced By Hot Melt Extrusion Technology For Dry Powder Inhalers, Ahmed Almotairy

Electronic Theses and Dissertations

The aim of the current investigation is to develop a sustained-release dry powder inhalation (DPI) formulation through continuous Hot Melt Extrusion (HME) process and see the impact of Sodium Bicarbonate (SB) and Mannitol (MAN) on the hydrophobic Eudragit RL PO (ERLPO) polymer. Ball milling and air-jet milling were utilized to have powder with a particle size range that is required for inhalation. Air-jet milled formulations shopromising particle size results compared to ball milled formulations. All solid-state characterization studies revealed no change on Theophylline (TH) crystallinity or occurrence of drug-excipient interactions in physical mixtures and formulations. X2 formulation released TH constantly …

Progress Toward The Synthesis Of 3-Methoxyflavones As Potential Antioxidants, Neuroprotective Agents, And Trifluoromethylated 19f Nmr Probes, Reem Alkhodier

Electronic Theses and Dissertations

The total synthesis of polyhydroxylated flavones have proven to be challenging, due to the presence of more than one hydroxyl group. Direct cyclization was not successful in any of the attempts. However, by using a silyl protecting group, the cyclization was feasible. Other reactions like the Friedel-Crafts acylation and selective protection of phenols were also difficult.

Synthesis Of Fluoroflavones As Potential Neuroprotective Agents, Maali Alshammari

Electronic Theses and Dissertations

Flavones are polyphenol natural products that are known to have neuroprotective effects against many diseases caused by the formation of reactive species. Flavonoids are subgroup of flavones and they are believed to function as antioxidants. Specifically, they target free radicals and eliminate its harmful effect on the cell. Fluoroflavones were designed to improve the potency of the antioxidant activity and potentially be used as neuroprotective agents. A monofluorinated and trifluoromethylated flavone were synthesized by using commercially available fluorination reagents, N-fluorobenzenesulfonimide; and Togni’s or Umemoto's respectively. After the synthesis of the desired flavones and their monofluorinated and trifluoromethylated derivatives, biological testing …

Design Of Thermosensitive Hydrogel For Extended-Release Of Praziquantel, Sheng Feng

Electronic Theses and Dissertations

Parasitic diseases are a severe threat to people and animals. Praziquantel is the most comanti-parasitic drug with high efficiency, and it has been used to treat parasitic diseases for many years. However, it has very strong gastrointestinal and liver metabolism that leads to a strong first-pass effect and a short half-life. Additionally, the frequent oral administration was inconvenient for the large livestock. To overcome these drawbacks, this study aimed to develop an extended-release thermosensitive hydrogel formulation that was applicable to the injectable administration. The praziquantel-loaded hydrogel formulation based on poloxamer 407 (20%, w/v) was prepared, and two strategies for modifications …

Development Of Controlled Release Oral Dosages By Density Gradient Modification Using 3d Printing Technologies, Zhiqing Hu

Electronic Theses and Dissertations

Over the years, three-dimensional (3D) printing has gradually become more comin people's lives. Due to its quick development, it has attracted the attention of researchers in the pharmaceutical industry. The main purpose of this project was to couple fused deposition modelling (FDM) 3D printing with hot melt extrusion (HME) technology to manufacture tablets with different drug release profiles and to solve dose issues related to an individual’s physiological differences and to enhance extended release properties. Ketoprofen was used as the model drug and different properties were added to the polymer to create a formulation suited to HME technology for the …

Development And Characterization Of Sustained-Release Formulations Via Novel Hot Melt Extrusion Techniques, Bjad Khalaf Almutairy

Electronic Theses and Dissertations

Hot melt extrusion (HME) is a leading technology that can be applied to many pharmaceutical preparations as solid dispersions. Part of this research project focus on injecting pressurized carbon dioxide (P-CO2) gas during the HME process. These combined techniques have an additional advantage of being adaptable and portable to a hot melt extruder instrument. The use of HME alongside with other techniques (P-CO2 or co extrusion process) for preparing an improved controlled/sustained release formulation is the main theme of this research project. Current research focusing on Active Pharmaceutical Ingredients (APIs) with good aqueous solubility requires novel approach to obtain tailored …

Role Of Glial Glutamate Transporter In Animal Model Of Acute And Chronic Inflammatory Pain, Ghallab Alotaibi

Electronic Theses and Dissertations

No abstract provided.

Nanosuspension Based Electrolyte Sensitive In Situ Gel For Topical Ocular Delivery Of Natamycin, Poorva H. Joshi

Electronic Theses and Dissertations

Natamycin (NT) is a commercially available antifungal drug used for the treatment of fungal keratitis, an infection which affects the clear corneal surface and its associated layers. Currently, NT is available commercially as a 5% w/v ophthalmic suspension, to be administered topically. The main objective of the present investigation was to develop and evaluate the natamycin loaded nanosuspension (NT-NS), as well as it’s corresponding in-situ gel (NT-NS-GG), for the treatment of fungal keratitis. NT-NS was prepared using homogenization technique and optimized based on size, PDI, zeta potential (ZP), assay and process stability. Further, optimized NT-NS was modified into an in-situ …

Formulation Development Of Natamycin Loaded Nanoemulsion For Ocular Drug Delivery, Kanika Goel

Electronic Theses and Dissertations

Natamycin (NT), also known as Pimaricin, is predominantly used as an anti-fungal medication for the treatment of fungal infections around the eye. The goal of the present study was to formulate and optimize NT loaded nanoemulsion (NT-NE) and examine its potential application in ophthalmic drug delivery. Placebos were evaluated with respect to particle size, PDI and ZP to identify the aqueous phase and lipid phase concentrations to be carried forward with NT-NE development. NT-NE were prepared by hot homogenization and ultra-probe sonication method, using Castor oil (CO) and Miglyol 812 as liquid lipids, Tween®80 and Poloxomer 188 as surfactants. NT-NE …

Formulation Strategies To Address Physiological And Anatomical Constraints For Improved Topical Ocular Drug Delivery, Karthik Yadav Janga

Electronic Theses and Dissertations

Delivery of therapeutic molecules to the eye has been a complicated task owing to its anatomical and physiological barriers. This dissertation delineates several formulation strategies to circumvent dynamic and static constraints hampering the ocular drug delivery. Advanced vesicular systems, bilosomes and transfersomes, were prepared to improve the ocular pharmacotherapy of natamycin (NT). NT bilosomes and transfersomes were further loaded into in situ gel systems which transformed immediately to hydrogel, in the simulated tear fluid, with good viscoelastic and mucoadhesive properties.In vitro corneal transport studies confirmed the superior permeability characteristics of NT from the optimized bilosome and transfersome in situ gel …

Development Of Continuous Manufacturing Process Of Acyclovir Ointment Using Hot-Melt Extrusion, Rui Wang

Electronic Theses and Dissertations

Hot-melt extrusion is a viable technology in preparing the pharmaceutical delivery system and has been considered as an attractive alternative to conventional processing methods. The objective of this study was to utilize the advantage of continuous manufacturing in HME to design and evaluate a formulation of topical semisolid ointment. Melt fusion ointments containing 5% of acyclovir (ACV) in water-soluble base with PEG 400, PEG 1500, and PEG 3350 polymers at various ratio were prepared. A design of experiment using I-optimal design was conducted. This design was used to study the influence of polymer ratio on the physicochemical properties of the …

Development Of Topical Oil/Peg Creams Of Voriconazole, Abhishek Shivashankar Shettar

Electronic Theses and Dissertations

Voriconazole (VRC) was selected as a model drug for preparation of Oil/PEG cream consisting of PEG 2000, PEG 400 and propylene glycol after performing drug-excipient compatibility studies. Twin screw processor with a 10 mm co-rotating twin screw configuration was used for preparation of oil/PEG creams. Creams prepared using twin-screw processor were characterized for the following: Differential Scanning Calorimetry (DSC), pH, Solvent activity (as)), viscosity, drug content uniformity, in vitro drug release testing (IVRT) and in vitro permeation testing (IVPT) using human cadaver skin. Creams are heterogenous biphasic semi-solid preparations consisting of oil and aqueous phases, wherein one phase is dispersed …

Implementing Mass Spectrometry For The Structural And Compositional Analysis Of Proteins, Mohammad Riaz

Electronic Theses and Dissertations

Lectins are sugar-binding proteins that perform various biological functions such as cellular recognition attachments etc. Pulses the dried edible seeds of certain plants are great sources of lectins and a proteomics approach directed at lectins identification would bring substantial improvement in the lectin identification process. Lectins from nine different plant species were analyzed through SDS-PAGE and proteomics analysis. After LC-MS/MS analysis proteins were identified with protein database searches using Uniprot. Functionally uncharacterized proteins were identified with database searches were annotated with the Pfam and NCBI-CCD databases. In-vitro pharmacological screening will be carried out to assess the pharmacological effects of these …

Community Pharmacists And Substance Use Disorders: Attitudes, Knowledge And Practices, Deepika Rao

Electronic Theses and Dissertations

Background: Substance use disorder (SUD) is a serious health concern affecting a large proportion of the US population. Community pharmacists are well-positioned to prevent, screen, and provide appropriate treatment for SUD. Stigma towards these patients and SUD results in reduced quality of care as well as poor treatment outcomes. It is imperative that pharmacists have the appropriate knowledge of and attitude towards prevention, harm reduction and treatment to develop therapeutic relationships and improve their delivery of pharmacy services

Objective: To assess knowledge, practices (with an emphasis upon screening), stigma and general attitudes of community pharmacists towards SUD and evaluate the …

Using An In Vitro-In Vivo Correlation For The ‘Bioequivalence By Design’ Development Of An Immediate Release Carbamazepine Product, Douglas Steinbach

Electronic Theses and Dissertations

The quality of a drug product may be characterized by the consistency with which its indicated clinical effect, and safety profile, is experienced by the patient. The concept that such quality should be built into a product is at the core of the United States Food and Drug Administration’s (FDA) quality by design (QbD) initiative. This vision for pharmaceutical product development emphasizes the risk-based identification of critical quality attributes (CQA) which summarize a product’s performance, the efficient refinement of critical product/process parameters (CPP) that can affect such attributes, and the systematic development of CPP limits, which assure appropriate performance of …

The Association Between Depression, Anxiety And Clinical Outcomes For Type 2 Diabetes Mellitus, Elham Heidari

Electronic Theses and Dissertations

Objective: To evaluate the impact of depression and/or anxiety on clinical outcomes of diabetes, including glycosylated hemoglobin (HgA1c), blood glucose, blood pressure, total cholesterol, weight and LDL among patients with incident type 2 diabetes mellitus (T2DM).

Method: A retrospective cohort study utilizing electronic medical record (EMR) data from a primary care physician (PCP) group practice was conducted to identify patients newly diagnosed with T2DM with at least 6 months pre-diagnosis and 12 months post-diagnosis of EMR data using International Classification of Disease 9th edition Clinical Modification (ICD-9-CM) coding. The presence of comorbid depression and anxiety was identified to identify four …

Characterization Of G-Protein Coupled Receptors In Pain, Depression And Anxiety, Neil Lax

Electronic Theses and Dissertations

Chronic pain and major depressive disorder are widespread conditions in the world. Interestingly, these conditions often occur comorbidly, with each individual disease amplifying the symptoms of the other. A significant amount of preclinical research in pain and depression focuses on G-protein coupled receptors (GPCRs), implying that GPCRs may be useful in treating this comorbidity. Our efforts have sought to characterize several poorly understood GPCRs, including the serotonin receptor subtypes 2C and 7 (5-HT2CR and 5-HT7R) and metabotropic glutamate receptor 5 (mGluR5), along with more well-known GPCRs such as the mu opioid receptor (MOR), and the role that they play in …

Synthesis Of Novel 6-Substituted And 5-Substituted Pyrrolo[2,3-D] Pyrimidine Antifolates As Targeted Anticancer Therapies, Xinxin Li

Electronic Theses and Dissertations

The dissertation will give an introduction, background and current research progress in the areas of antifolates and chemotherapy of anticancer. The design and synthesis of classical 6- substituted pyrrolo[2,3-d]pyrimidines and 5-substituted pyrrolo[2,3-d]pyrimidines as potential antifolates have been described. The design variations include: methylated thiophene regioisomers, fluorinated phenyl regioisomers, thionyl regioisomers on the side chain of pyrrolo[2,3-d]pyrimidines. As a part of this study, a series of new compounds have been synthesized and characterized. Of these, ten final compounds were submitted for biological evaluation.

The Influence Of Age, Gender, And Thiol Repletion In An In Vivo Model Of Lewy Body Disorders, Daniel Mason

Electronic Theses and Dissertations

Lewy body disorders are a family of neurological brain disorders associated with olfactory, motor, and cognitive deficits and are collectively defined as α-synucleinopathies, as they are characterized by hallmark “Lewy bodies” composed of aggregated, fibrillar α-synuclein. It is not certain but often posited that fibrillar α-synuclein seeds the progressive, self-propagating spread of Lewy pathology through neuroanatomical circuitry. Furthermore, the site of disease induction is still debated. In Aim I, we developed a novel protocol for generating reproducible and robust α-synucleinopathy in the limbic temporal lobe following infusions of preformed α-synuclein iv fibrils into the mouse olfactory bulb, which is frequently …

Influence Of Bilberry-Derived Anthocyanidins On Key Regulators Of Colorectal Cancer Development., Ashley M. Mudd

Electronic Theses and Dissertations

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths within the United States. A variety of factors including exposure to environmental carcinogens, such as benzo[a]pyrene (B[a]P), dysbiosis of the gut microbiome and hereditary influences, including APC mutations, have been shown to lead to an increased risk of developing colorectal cancer. Given the recent alarming rise in cases of colorectal cancer diagnosed in individuals under the age of 40, further insight into developing novel and effective prevention and treatment strategies are warranted. The family of plant pigments known as the anthocyanins has been identified with …

Self-Assembling Bioaffinity Hydrogels For Localized Antibody Delivery, Wen Liu

Electronic Theses and Dissertations

The scope of illnesses that are being treated using monoclonal antibodies (mAbs) has been expanding from cancers to autoimmune diseases due to their high specificity to their molecular target. Because many of the new mAbs are aimed to modulate the immune system, an emerging concern is that patients with chronic illnesses are subjected to immune-related Adverse Events (irAEs). Loss of immunological tolerance to self-antigens or increased susceptibility to infections have been documented in some mAb treatments. Localized sustained release of mAb at disease sites might mitigate the risk of such toxicities. Antibody drugs are formulated typically for parenteral delivery because …

Effects Of Natural Antioxidants On Motor And Cognitive Deficits In An Animal Model Of Aging And Obesity And Dopaminergic-Like Sh-Sy5y Cell Line, Sneha Potdar

Electronic Theses and Dissertations

Aging is a universal phenomenon. One of the greatest challenges faced by the elderly population is to sustain a healthy standard of living. Advancing age is associated with increased motor and cognitive deficits. Loss of balance, falls, hip fractures, and poor memory all contribute to a decline in the quality of life of the aging population. While ongoing research is making advances to find therapeutic interventions for neurodegenerative disorders like Parkinson’s and Alzheimer’s diseases, there is a pressing need to address deficits associated with normal aging.

Increase in oxidative stress and a decline of antioxidant mechanisms with aging have been …

A Clinically Relevant Mouse Model Of Cisplatin-Induced Kidney Injury., Cierra Nichole Sharp

Electronic Theses and Dissertations

Cisplatin is a potent chemotherapeutic used for the treatment of many solid cancers, including testicular, ovarian, and lung cancer. Cisplatin causes many adverse side effects, of which nephrotoxicity leading to acute kidney injury is dose-limiting. Approximately 30% of patients will develop nephrotoxicity with cisplatin, and will either have their next dose of cisplatin lowered, skipped, or be switched to a less nephrotoxic chemotherapeutic altogether. These outcomes are not ideal when trying to treat cancer. Previously, it was believed that patients could recover from cisplatin-induced acute kidney injury with little to no lasting effects, but recent longitudinal studies have shown this …

Hiv Integrase Inhibitor Pharmacogenetics And Clinical Outcomes: An Exploratory Association Study, Derek E. Murrell

Electronic Theses and Dissertations

As HIV is now primarily a chronic condition, treatment is given life-long with changes as necessitated by alterations in tolerability and efficacy. Thus, personalized medicine may be useful in the prevention of unnecessary drug exposure and avoidable side effects. Three of the four currently available HIV integrase strand transfer inhibitors (INSTIs), raltegravir, elvitegravir, and dolutegravir, are widely utilized antiretrovirals in the USA and exhibit variations in outcomes among subjects. To interrogate differences among subjects receiving these drugs, we investigated the association of several single nucleotide polymorphisms (SNPs) with drug exposure, clinical outcomes, and subject-reported adverse events. HIV+ adults (≥18 years …

The Association Between Medication Adherence In Mental Illness And Substance Use Disorder Relapse In Patients With Dual Diagnosis, Tyler Dunn

Electronic Theses and Dissertations

Objectives: The aims of the study were to (1) identify personal, social, and clinical history for patients with substance use disorder (SUD) and mental illness, (2) measure agreeance between patient self-report versus facility record history for mental illness, substance abuse, and psychotropic medication, (3) investigate the specific role of medication adherence and barriers to use for psychotropic medications upon SUD relapse, and (4) assess follow-up changes in mental illness severity and medication adherence in dual diagnosis patients enrolled in a substance abuse rehabilitation program.

Methods: The pilot study utilized a mixed methodology. Inclusion criteria included male patients at least 18 …

Designing A Calibration Set In Spectral Space For Efficient Development Of An Nir Method For Tablet Analysis, Md Anik Alam

Electronic Theses and Dissertations

Designing a calibration set is the first step in developing a spectroscopic calibration method for quantitative analysis of pharmaceutical tablets. This step is critical because successful model development depends on the suitability of the calibration data. For spectroscopic-based methods, traditional concentration based techniques for designing calibration sets are prone to have redundant information while simultaneously lacking necessary information for a successful calibration model. The traditional method also follows the same design approach for different spectroscopic techniques and different formulations, thereby lacks the optimizing capability to be technique and formulation specific.

A method for designing a calibration set in the Near …

Synthesis Of Novel 5-Substituted Pyrrolo[2,3-D]Pyrimidine Antifolates As Selective And Potent Anti-Tumor Agents, Mohammad Karim

Electronic Theses and Dissertations

In last few decades many folate analogs have been discovered and several compounds are successfully being used as anticancer agents. Methotrexate (MTX), pemetrexed (PMX), raltitrexed (RTX): are a few examples of classical antifolates that are currently in clinical use. Although these compounds are widely used, all of them show dose limiting toxicity due to their non-specific transport into normal cells as well as malignant cells. Currently, clinically used classical antifolates suffer from this disadvantage because there is no way to selectively transport them into malignant cells. Currently available antifolates are transported via reduced folate career (RFC) as well as Folate …

The Combined Neuropharmacology And Toxicology Of Major 'Bath Salts' Constituents Mdpv, Mephedrone, And Methylone, Serena Allen

Electronic Theses and Dissertations

The synthetic cathinones, 3,4- methylenedioxypyrovalerone (MDPV), 4-methylmethcathinone (mephedrone), and 3,4- methylenedioxymethcathinone (methylone), gained worldwide notoriety as the psychoactive components of ‘bath salts;’ a marketing term used to circumvent federal drug laws and permit their legal sale. Previous studies have shown that these drugs share pharmacological characteristics with cocaine and the amphetamines, however, descriptions of their neurotoxic properties are limited. Moreover, while forensic analysis has revealed that the most frequently abused bath salts ‘brands’ contain binary and ternary mixtures of MDPV, mephedrone, and methylone, the majority of preclinical research has focused on explicating the individual effects of these drugs. Therefore, the …

Synthetic Investigation Of Natural Products Causing Dopaminergic Neurodegeneration, Michael John Cunningham

Electronic Theses and Dissertations

The terrestrial organisms Streptomyces venezuelae and Rhaponticum repens produce toxic secondary metabolites that likely function as chemical deterrents. The polyketide SV-6 from S. venezuelae and the sesquiterpene lactone repin from R. repens both produce dose-dependent and selective degeneration of dopaminergic neurons. These molecules represent two possible tools that can be used to explore chemotoxic induction of Parkinson’s disease. In the case of SV-6, a newly isolated metabolite, total synthesis was undertaken to confirm its structure and biological activity. The natural product was produced from methacrolein and Roche ester starting materials that were elaborated to their respective fragments, a vinyl iodide …

The Role Of Brand Name Fluency: A Pharmaceutical Marketing Perspective, David Wamble

Electronic Theses and Dissertations

Background: consumers are exposed to thousands of advertisements, most all of which are designed to promote a particular brand and accompanying brand name. The selection of a brand name is a critical strategic decision and is an important means to building brand equity. The importance of branding elements, specifically brand names, has led pharmaceutical manufacturers to become more creative and open the possibilities of language in brand name development. Given the complexities associated with brand name development in the U.S. pharmaceutical industry and the trends observed in recent pharmaceutical brand names, advancing the understanding of how brand name selection can …